1937 Nobel Prize in Physiology or Medicine – Szent-Györgyi

What You Will Learn in This Article

Discover how the cause of scurvy, known for centuries, was definitively identified at a molecular level through experiments using kilograms of paprika, and how the discoverer later became a spy, feeding information about Hungarian resistance to the Nazis to Churchill.

Why Did an Orange Save a Person?

Scurvy is an ancient disease in human history. It repeatedly appeared in conditions with a lack of fresh vegetables and fruits, especially during long sea voyages. Symptoms include swollen, bleeding gums, wounds that do not heal, and eventual death. It was the leading cause of death among European sailors during the Age of Exploration.

In the 18th century, James Lind, a British naval surgeon, confirmed through clinical trials that citrus fruits prevent the disease, but he did not know exactly what in them was effective. Lime juice became a standard part of the British Navy’s diet, earning the British the nickname "Limey," but the identity of the substance remained a mystery for 200 years.

In 1928, a Hungarian scientist began to purify a reducing substance from various foods, including beef glands, oranges, and cabbage. He initially called this substance "hexuronic acid," but it was soon identified as vitamin C – ascorbic acid, as we know it today.

His crucial breakthrough surprisingly came from his home kitchen. More details will be provided later.

The Landscape of the Era – Rehearsals for Massacres

1937 was a year when war had already begun in several parts of the world.

On April 26, the Nazi Condor Legion bombed Guernica, Spain. This was the first instance in human history of an entire city being subjected to indiscriminate bombing. Picasso’s Guernica depicts this event. This bombing technique served as a rehearsal for the methods that would soon devastate European cities.

On July 7, the Marco Polo Bridge Incident marked the beginning of the Second Sino-Japanese War. Japan began its invasion of mainland China. The Nanjing Massacre in December of that year etched the nature of this war into the world’s memory. This war would escalate into the Pacific War eight years later, eventually ending with the dropping of atomic bombs.

In November, Nazi Germany, Italy, and Japan formed the Axis through the Anti-Comintern Pact. This would later be expanded into a formal military alliance three years later.

The Soviet Great Purge reached its peak in this year. Half of the military leadership, a significant portion of the Politburo, and many intellectuals were executed or sent to the Gulag. This was a period when Stalin destroyed the very people who had created his regime in order to ensure its security.

When viewed in the context of Korean history, 1937 was the year when the Second Sino-Japanese War began, and the transition to a total mobilization system in Korea also commenced. This included the forced conscription and mobilization of Korean youth, the forced requisition of supplies, and the expansion of mandatory shrine visits. In the same year that the identity of vitamin C was revealed in Europe, young Koreans were facing the beginning of their forced conscription as soldiers. While the physiology of the human body was being revealed, the human body was simultaneously being consumed as a weapon.

The Story of the Man – From the Land of Paprika

Albert Szent-Györgyi was born in Budapest in 1893. He came from a distinguished Hungarian scientific family. His uncle was already an accomplished physiologist, and he grew up in the laboratory.

A Scar from World War I

During World War I, he served as a military doctor in the Austro-Hungarian army. After spending three years on the horrific front lines, he shot himself in the arm in order to be able to live as a researcher. This self-inflicted wound led to his transfer to a rear hospital and, subsequently, to his return to research. This decision changed the course of his life.

This extreme decision reveals his character. He was a man who made drastic decisions in extreme situations to determine the direction of his life. This characteristic would resurface during his involvement in the anti-Nazi resistance during World War II.

The Discovery of Paprika

Around 1928-1932, while at Cambridge and Minnesota, he purified an unknown reducing substance from beef glands, oranges, and cabbage. He initially called this substance "hexuronic acid," but other researchers identified it as the anti-scurvy factor (vitamin C). This substance was given a new name, ascorbic acid – meaning "that which removes scurvy."

However, there was a major problem. The quantities were too small. A hundred kilograms of beef gland yielded only a few grams of ascorbic acid. In his laboratory, he lacked sufficient quantities for the next stage of experiments.

After he returned to the University of Szeged in Budapest in 1932, his wife prepared paprika (bell pepper) for dinner one evening. He did not particularly like paprika. He decided to take the paprika to the laboratory to analyze it. This was a convenient excuse to avoid eating his dinner.

The results were surprising. Paprika contained several times more vitamin C than oranges. Hungary was a major producer of paprika. He began to purify kilograms of ascorbic acid from paprika. This is perhaps a unique case of a single laboratory using a national industry to solve its own problem.

This large-scale purification was crucial. With sufficient quantities of pure substance, subsequent research, such as determining the precise chemical structure, elucidating the metabolic pathways, and conducting clinical trials, could proceed rapidly.

Biological Oxidation – His Second Major Discovery

Szent-Györgyi's Nobel Prize actually recognized two achievements together: vitamin C, as well as "the elucidation of the biological oxidation process, in particular, the role of fumaric acid."

At the time, how cells used oxygen to completely oxidize glucose was an unresolved problem. Warburg's 1931 discovery illuminated the final step (cytochrome oxidase), but the previous step – the intermediate step in which glucose is oxidized to CO2 – remained a mystery.

While experimenting with muscle tissue, Szent-Györgyi demonstrated that organic acids such as fumaric acid, succinic acid, and malic acid were involved in this oxidation process. Adding one of these organic acids to the tissue greatly increased the cell's oxygen consumption.

This discovery soon expanded into the Krebs cycle (Krebs formalized it in 1937, and was awarded the Nobel Prize in 1953). Today, the high school biology diagram of the Krebs cycle shows fumaric acid, succinic acid, and malic acid. Szent-Györgyi's muscle experiments were the first to definitively confirm that these were essential intermediates in the cycle.

Key Achievements – Cellular Metabolism as Seen Through Catalysts

Molecules That Cycle Within the Cycle

The fundamental principle behind what Szent-Györgyi revealed is that cellular metabolism is organized in cycles.

Glucose oxidation is not a linear reaction. A series of intermediates (citrate → isocitrate → α-ketoglutarate → succinate → fumarate → malate → oxaloacetate → back to citrate) are linked in a cycle, and each time the cycle completes, a new glucose molecule enters, and it is broken down into CO2 and H2O. The intermediates of the cycle are not consumed but are repeatedly reused.

The CS analogy naturally applies here. This is similar to the reused catalysts and middleware.

What happens when a web server processes a request:

• A new request arrives
• Authentication middleware, logging middleware, error handlers, etc., process this request
• A response is returned

The remarkable thing is that the middleware itself is not consumed. A single authentication middleware can process thousands of requests per second, and it remains unchanged. A reusable component that handles an infinite stream of requests.

The Krebs cycle works on exactly the same principle. Each of the intermediates in the cycle (such as fumaric acid) acts like a reusable catalyst. Each time a new glucose molecule enters the cycle, these intermediates help oxidize it, and then return to their original state after completing the cycle. A remarkable structure in which a small amount of catalytic molecules can process a large amount of glucose.

However, this analogy breaks down here. Software middleware is something we explicitly design, and the logic of each step is clear. The Krebs cycle was created by evolution, and why these particular eight intermediates were selected, and not other alternatives, remains partially an open question. Other metabolic cycles (alternative metabolic pathways) are also found in various organisms. Our system is one of the many possibilities that has evolved very successfully.

Is Vitamin C Itself a Catalyst?

The role of vitamin C in cells is also catalytic. Ascorbic acid acts as a cofactor in various oxidation reactions within cells, cycling between oxidized and reduced states. A single ascorbic acid molecule can assist in many reactions over several cycles.

This explains why only about 100 mg of vitamin C per day is sufficient for humans to survive. If it were consumed in each reaction and disappeared, several kilograms would be needed. However, because it acts as a catalyst, a very small amount is sufficient.

The Anti-Nazi Resistance and Churchill

Szent-Györgyi's activities during World War II were as dramatic as his scientific achievements.

In 1943, he was sent to Switzerland with the approval of the Hungarian government. On the surface, it was a scientific conference, but the real purpose was to secretly contact the Allies as a special envoy of the Hungarian government. Hungary was nominally an ally of Nazi Germany, but Prime Minister Miklós Kállay wanted to break away from this alliance and move towards the Allies.

When Szent-Györgyi contacted a British intelligence officer (SOE) in Istanbul, it was discovered by the Nazi intelligence service. There is a record that Hitler personally ordered his arrest. He returned to Budapest and hid in hiding for several months.

During this period, he was already a Nobel laureate. His world-renowned reputation offered some protection, but the Nazi Gestapo, undeterred, held his wife and daughter hostage. He remained in hiding until early 1945, when Soviet troops occupied Budapest.

After the war, he moved to the United States in 1947, as the Soviet domination of Hungary became clear. His life, spanning the extremes of the 20th century, as a Nobel laureate, a non-Jewish Hungarian, and a member of the anti-Nazi resistance, is a story in itself.

Why Is It Important?

Szent-Györgyi's Nobel Prize remains relevant today on three levels.

Public Health Level: With the identification and large-scale production methods of vitamin C, scurvy has been eradicated worldwide. Today's multivitamins, fortified foods, and prenatal prescriptions – all have their roots in the laboratory at the University of Szeged where ascorbic acid was purified from paprika.

Metabolic Level: With the completion of the Krebs cycle, the entire map of cellular energy metabolism has been completed. Today's diabetes, mitochondrial diseases, and metabolic syndromes – all of these diseases are understood as defects at specific points in this cycle.

Science and Politics Level: A case where a Nobel laureate used his reputation to participate in political resistance. He was one of the pioneers of a trend that would later be followed by several scientists (Sakharov, Pauling, Pauza, etc.).

He left us with the following lesson: "When resources are scarce, use local specialties." The decisive material that led to his world-class discovery was Hungarian paprika. The perspective of connecting local abundance to global problems – this was his pragmatism. Today, this principle applies in software and startups as well. The creativity of making the most of the resources one has access to is often more powerful than having unlimited access to new resources.

Even as you read this sentence, the Krebs cycle is turning in the cells of your body. The map of this cycle began to be drawn 90 years ago in the paprika purification laboratory in Budapest.

Summary of Vitamin C and Biological Oxidation: Szent-Györgyi purified vitamin C in large quantities from paprika and elucidated its metabolic role, and demonstrated that fumaric acid and other organic acids were involved in cellular oxidation cycles through experiments with muscle tissue. This latter discovery soon expanded into the Krebs cycle, completing the entire map of cellular energy metabolism.

→ Experience it with code: DevBench – Middleware and Reusable Catalyst Components → Learn about CS concepts: DryBench – Cyclic Data Structures and Reuse